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In this study, we use multiple rodent and human brain tissue and neural cell models to demonstrate that CLU is expressed as multiple isoforms that have distinct cellular or subcellular localizations in the brain. Of particular significance, we identify a non-glycosylated 45 kDa CLU isoform (mitoCLU) that is localized to the mitochondrial matrix and expressed in both rodent and human neurons and astrocytes. In addition, we show that rodent mitoCLU is translated from a non-canonical CUG (Leu) start site in Exon 3, a site that coincides with an AUG (Met) in human CLU. Last, we reveal that mitoCLU is present at the gene and protein level in the currently available CLU\u2013\/\u2013 mouse model. Collectively, these data provide foundational knowledge that is integral in elucidating the relationship between CLU and the development of LOAD.<\/jats:p>","DOI":"10.7554\/elife.48255","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T09:00:12Z","timestamp":1574067612000},"source":"Crossref","is-referenced-by-count":56,"title":["Brain clusterin protein isoforms and mitochondrial localization"],"prefix":"10.7554","volume":"8","author":[{"given":"Sarah K","family":"Herring","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Jung","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Punam","family":"Rawal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anindit","family":"Chhibber","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0491-6943","authenticated-orcid":true,"given":"Liqin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, United States"},{"name":"Neuroscience Graduate Program, University of Kansas, Lawrence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2019,11,18]]},"reference":[{"key":"bib1","article-title":"Alzgene - Top Results","author":"Alzforum Networking","year":"2019","unstructured":"Alzforum Networking. 2019. 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